Tuberculosis (TB) remains a global health emergency, responsible for 8.6 million new cases and 1.3 million deaths in 2012. The Stop TB Partnership has set very ambitious targets that include a 50% reduction in TB incidence from 2015 to 2025. Strategies to find people with active TB earlier in their disease course must therefore be rapidly scaled up if TB control targets for 2025 are to be approached. However, active case finding (ACF) for TB is expensive and difficult to implement in practice and the ideal approach to ACF will differ from one epidemiological setting to the next. Rural settings represent a critical knowledge gap in this regard: despite TB incidence in rural areas rivaling that in large cities, ACF is generally seen as infeasible in rural areas due to infrastructure and resource constraints. In sub-Saharan Africa, 60% of the population still lives in rural settings; thus, TB i Africa cannot be controlled by focusing on cities alone. This proposed research is a novel study of the comparative effectiveness, cost-effectiveness, and implementation of three strategies for active TB case finding in rural South Africa. The proposed study is a cluster-randomized comparative effectiveness study involving 56 clinics in the rural district of Vhembe, South Africa - a district with a TB incidence of 350 per 100,000/year. Two comparisons will be made: (1) A parallel comparison (28 clinics each) of augmented facility-based TB screening (sputum collection and Xpert MTB/RIF testing of all coughing patients presenting to clinic for any reason) versus contact investigation of active TB cases; and (2) A cluster- crossover evaluation within the contact investigation arm, comparing traditional household contact tracing versus incentive-based tracing (giving airtime vouchers in exchange for contact referrals presenting at the clinic). The specific aims of this research are: (1) To evaluate acceptability and adoption of active TB case finding strategies in rural South Africa; (2) To describe the comparative implementation of facility-based screening and contact investigation; (3) To measure the comparative effectiveness of active TB case-finding in a rural, high-burden setting; (4) Evaluate the comparative costs and cost-effectiveness of each case-finding strategy. This multidisciplinary research represent an innovative path toward achieving medium-term TB control targets in a key epidemiological setting (i.e., rural Africa), but this study can also serve as a methodological example of how to improve real-world decision-making across a broad array of other fields in the context of urgent and ambitious population health priorities.